EZH2 regulates oncomiR-200c and EMT markers in esophageal squamous cell carcinomas

Abstract EZH2, as a histone methyltransferase, has been associated with cancer development and metastasis possibly through the regulation of microRNAs and cellular pathways such as EMT. In this study, the effect of EZH2 expression on miR-200c and important genes of the EMT pathway was investigated i...

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Main Authors: Fatemeh Nourmohammadi, Mohammad Mahdi Forghanifard, Mohammad Reza Abbaszadegan, Vajiheh Zarrinpour
Format: Article
Language:English
Published: Nature Portfolio 2022-10-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-022-23253-2
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author Fatemeh Nourmohammadi
Mohammad Mahdi Forghanifard
Mohammad Reza Abbaszadegan
Vajiheh Zarrinpour
author_facet Fatemeh Nourmohammadi
Mohammad Mahdi Forghanifard
Mohammad Reza Abbaszadegan
Vajiheh Zarrinpour
author_sort Fatemeh Nourmohammadi
collection DOAJ
description Abstract EZH2, as a histone methyltransferase, has been associated with cancer development and metastasis possibly through the regulation of microRNAs and cellular pathways such as EMT. In this study, the effect of EZH2 expression on miR-200c and important genes of the EMT pathway was investigated in esophageal squamous cell carcinoma (ESCC). Comparative qRT-PCR was used to examine EZH2 expression in ESCC lines (YM-1 and KYSE‐30) following the separately transfected silencing and ectopic expressional EZH2 vectors in ESCC. Subsequently, expression of miR-200c and EMT markers was also assessed using qRT-PCR, western blotting and immunocytochemistry. Underexpression of Mir200c was detected in YM-1 and KYSE-30 cells after EZH2 silencing, while its overexpression was observed after EZH2 induced expression. Following EZH2 silencing, downregulation of mesenchymal markers and upregulation of epithelial markers were detected in the ESCCs. Our results demonstrate that EZH2 regulates the expression of miR-200c and critical EMT genes, implying that overexpression of Zeb2, Fibronectin, N-cadherin, and Vimentin lead to a mesenchymal phenotype and morphology while underexpression of epithelial genes, enhance cell migration after enforced expression of EZH2 in ESCCs. EZH2 gene can be a beneficial treatment marker for patients with esophageal cancer through decrease invasiveness of the disease and efficient response to neoadjuvant therapy.
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spelling doaj.art-3867ae2361bb4b398c3493ffc3ff6bcd2022-12-22T03:40:01ZengNature PortfolioScientific Reports2045-23222022-10-0112111310.1038/s41598-022-23253-2EZH2 regulates oncomiR-200c and EMT markers in esophageal squamous cell carcinomasFatemeh Nourmohammadi0Mohammad Mahdi Forghanifard1Mohammad Reza Abbaszadegan2Vajiheh Zarrinpour3Department of Biology, Damghan Branch, Islamic Azad UniversityDepartment of Biology, Damghan Branch, Islamic Azad UniversityMedical Genetics Research Center, Mashhad University of Medical SciencesDepartment of Biology, Damghan Branch, Islamic Azad UniversityAbstract EZH2, as a histone methyltransferase, has been associated with cancer development and metastasis possibly through the regulation of microRNAs and cellular pathways such as EMT. In this study, the effect of EZH2 expression on miR-200c and important genes of the EMT pathway was investigated in esophageal squamous cell carcinoma (ESCC). Comparative qRT-PCR was used to examine EZH2 expression in ESCC lines (YM-1 and KYSE‐30) following the separately transfected silencing and ectopic expressional EZH2 vectors in ESCC. Subsequently, expression of miR-200c and EMT markers was also assessed using qRT-PCR, western blotting and immunocytochemistry. Underexpression of Mir200c was detected in YM-1 and KYSE-30 cells after EZH2 silencing, while its overexpression was observed after EZH2 induced expression. Following EZH2 silencing, downregulation of mesenchymal markers and upregulation of epithelial markers were detected in the ESCCs. Our results demonstrate that EZH2 regulates the expression of miR-200c and critical EMT genes, implying that overexpression of Zeb2, Fibronectin, N-cadherin, and Vimentin lead to a mesenchymal phenotype and morphology while underexpression of epithelial genes, enhance cell migration after enforced expression of EZH2 in ESCCs. EZH2 gene can be a beneficial treatment marker for patients with esophageal cancer through decrease invasiveness of the disease and efficient response to neoadjuvant therapy.https://doi.org/10.1038/s41598-022-23253-2
spellingShingle Fatemeh Nourmohammadi
Mohammad Mahdi Forghanifard
Mohammad Reza Abbaszadegan
Vajiheh Zarrinpour
EZH2 regulates oncomiR-200c and EMT markers in esophageal squamous cell carcinomas
Scientific Reports
title EZH2 regulates oncomiR-200c and EMT markers in esophageal squamous cell carcinomas
title_full EZH2 regulates oncomiR-200c and EMT markers in esophageal squamous cell carcinomas
title_fullStr EZH2 regulates oncomiR-200c and EMT markers in esophageal squamous cell carcinomas
title_full_unstemmed EZH2 regulates oncomiR-200c and EMT markers in esophageal squamous cell carcinomas
title_short EZH2 regulates oncomiR-200c and EMT markers in esophageal squamous cell carcinomas
title_sort ezh2 regulates oncomir 200c and emt markers in esophageal squamous cell carcinomas
url https://doi.org/10.1038/s41598-022-23253-2
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AT mohammadrezaabbaszadegan ezh2regulatesoncomir200candemtmarkersinesophagealsquamouscellcarcinomas
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